The use of osteoinductive proteins or growth factors, such as bone morphogenetic proteins (BMPs), mitogenic growth factors, etc., improves clinical outcomes after surgical reconstruction of skeletal defects (e.g., implants). Such osteoinductive factors induce bone formation by targeting and activating undifferentiated perivascular connective tissue cells. Mitogenic growth factors target and accelerate the osteogenic activity of previously differentiated cells. Although advances have improved the biological activity of osteoinductive factors, their clinical application has been limited by the requirement for a superior tissue scaffold/delivery vehicle.
Autologous bone grafts are the gold standard for restoring skeletal defects because they provide both a natural tissue scaffold and osteoinductive growth factors. Allogenic grafts may also be used, such as demineralized bone matrices. For example, demineralized bone material can be prepared by grinding a bone, demineralizing it with an acid solution, washing with a phosphate buffered solution, washing with ethanol and drying it. Demineralized bone material can also be obtained from a commercial bone or tissue bank (e.g., AlloSource, Denver Colo.). Because autogenic and allogenic sources of human bone are limited and may be expensive or painful to obtain, the use of substitute materials is preferred. Numerous synthetic or modified natural materials have been experimentally evaluated as alternative delivery vehicles, and include but are not limited to products containing hydroxyapatites, tricalcium phosphates, aliphatic polyesters (poly(lactic) acids (PLA), poly(glycolic)acids (PGA), polycaprolactone (PCL), cancellous bone allografts, human fibrin, plaster of Paris, apatite, wollastonite (calcium silicate), glass, ceramics, titanium, devitalized bone matrix, non-collagenous proteins, collagen and autolyzed antigen extracted allogenic bone. However, these synthetic or modified natural materials have yet to result in delivery vehicles having osteoinductivity comparable to autograft or allograft bone sources, or having the capability to enhance the osteoinductivity of these or other osteoinductive materials.
Alternate products are desirable.